RESEARCH BRIEF: An Examination of the Social and Clinical Influences in Prostate Cancer Treatment in African American and White Men

BACKGROUND: The death rate for prostate cancer (PrCA), the most commonly diagnosed cancer in African-American (AA) men, is twice the rate of European-American (EA) men. AA men in South Carolina have the highest age-adjusted death rate in the nation. Studies have shown that treatment offered to AA men with PrCA is systematically different from that offered to EA men. METHODS: Surveys were mailed to 1,866 men in South Carolina with a diagnosis of PrCA. South Carolina men diagnosed with PrCA between 1996 and 2002 were eligible to participate. We performed a descriptive assessment of the factors that influenced PrCA treatment decisions. RESULTS: The treatment choices of AA men were significantly more likely to be influenced by pain and significantly less likely to be influenced by potential for cure compared to EA men. CONCLUSIONS: Providers must be cognizant of the factors that influence treatment, particularly in AA men. Despite the national undertaking to eliminate health disparities, the United States is far from implementing a comprehensive focus on the health of AA men, despite their elevated PrCA morbidity and mortality rates

Alvin J. Siteman Cancer Center: Cancer prevention perspective

We summarize Siteman Cancer Center catchment that covers 82 counties in southern Illinois and eastern Missouri. We note both the high poverty and cancer rates in many rural counties. Siteman Community Outreach and Engagement has developed a number of strategies to move towards achieving health equity. These include NCI-funded research projects in rural clinics and outreach to improve access to cancer prevention services. To increase capacity for community-engaged research, we have developed and refined a Community Research Fellows Training Program

Social and clinical predictors of prostate cancer treatment decisions among men in South Carolina

OBJECTIVE: To assess social and clinical influences of prostate cancer treatment decisions among white and black men in the Midlands of South Carolina. METHODS: We linked data collected on treatment decision making in men diagnosed with prostate cancer from 1996 through 2002 with clinical and sociodemographic factors collected routinely by the South Carolina Central Cancer Registry (SCCCR). Unconditional logistic regression was used to assess social and clinical influences on treatment decision. RESULTS: A total of 435 men were evaluated. Men of both races who chose surgery (versus radiation) were more likely to be influenced by their physician and by family/friends. Black men who chose surgery also were ~5 times more likely to make independent decisions (i.e., rather than be influenced by their doctor). White men who chose surgery were twice as likely to be influenced by the desire for cure and less likely to consider the side effects of impotence (odds ratio (OR) = 0.40; 95% confidence interval (CI): 0.18, 0.88) and incontinence (OR = 0.27; 95% CI: 0.12, 0.63); by contrast, there was a suggestion of an opposite effect in black men, whose decision regarding surgery tended to be more strongly influenced by these side effects. CONCLUSION: Results suggest that both clinical and social predictors play an important role for men in choosing a prostate cancer treatment, but these influences may differ by race

Two novel susceptibility loci for prostate cancer in men of African ancestry

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5\u27 of the gene IRS2 and 3\u27 of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk

A germline variant at 8q24 contributes to familial clustering of prostate cancer in men of African ancestry

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age \u3c60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening

Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling

T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are required to maintain human T cell proliferative capacity through the STAT5 signaling pathway. T cells from humanized mice proliferate better if stimulated in the presence of human IL-7 or IL-15 or if T cells are exposed to human IL-7 or IL-15 in mice. Freshly isolated T cells from human peripheral blood lose proliferative capacity if cultured for 24 hours in the absence of IL-7 or IL-15. We further show that phosphorylation of STAT5 correlates with proliferation and inhibition of STAT5 reduces proliferation. These results reveal a novel role of IL-7 and IL-15 in maintaining human T cell function, provide an explanation for T cell dysfunction in humanized mice, and have significant implications for in vitro studies with human T cells

Secondary consent to biospecimen use in a prostate cancer biorepository

BACKGROUND: Biorepository research has substantial societal benefits. This is one of the few studies to focus on male willingness to allow future research use of biospecimens. METHODS: This study analyzed the future research consent questions from a prostate cancer biorepository study (N = 1931). The consent form asked two questions regarding use of samples in future studies (1) without and (2) with protected health information (PHI). Yes to both questions of use of samples was categorized as Yes-Always; Yes to without and No to with PHI was categorized as Yes-Conditional; No to without PHI was categorized as Never. We analyzed this outcome to determine significant predictors for consent to Yes-Always vs. Yes-Conditional. RESULTS: 99.33 % consented to future use of samples; 88.19 % consented to future use without PHI, and among those men 10.2 % consented to future use with PHI. Comparing Yes Always and Yes Conditional responses, bivariate analyses showed that race, family history, stage of cancer, and grade of cancer (Gleason), were significant at the α = 0.05 level. Using stepwise multivariable logistic regression, we found that African–American men were significantly more likely to respond Yes Always when compared to White men (p < 0.001). Those with a family history of prostate cancer were significantly more likely to respond Yes Always (p = 0.002). CONCLUSIONS: There is general willingness to consent to future use of specimens without PHI among men

The burden of prostate cancer in Trinidad and Tobago: One of the highest mortality rates in the world

PURPOSE: In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world. METHODS: 6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography. RESULTS: The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively). CONCLUSIONS: Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report